The objectives of the proposed research are to identify the genes controlling chromosome replication during meiosis; and to determine the role of these genes in the biochemical reactions of replication. On the basis of considerable existing evidence, we propose that meiotic replication is governed by two distinct types of genes. One group of genes controls replication-reactions unique to meiosis, the other group controls replication-reactions which are identical in meiotic and mitotic cells. Our first objective is to identify both types of genes; this is accomplished by characterizing two distinct types of temperature-sensitive, replication deficient mutants (in Saccharomyces cerevisiae). The first group of mutants carry out normal mitotic replication but are defective in replication during meiosis. After genetic analysis to determine dominance and segregation, suitable mutants are organized into a minimum number of functional groups (genes) by genetic complementation tests; these genes control replication reactions unique to meiosis. The second group of mutants are defective in replication during mitosis and they have already been assigned to individual genes. We now propose to re-examine these mutants to identify those lesions which cause equivalent defects in replication during meiosis; such mutants identify genes controlling identical replication reactions in meiotic and mitotic cells. Our second objective is identification of the biochemical reactions controlled by each gene. This begins with a determination of execution points, representing the time of completion of an essential gene-function. Genes with execution points coincident with replication are further analyzed in synchronous meiotic cultures, for the effects of the restrictive-temperature on the kinetics of DNA synthesis. This provides a preliminary division of the genes into those which control precursor (deoxynucleotide) formation or polymerization from those controlling replication initiation.